Variant chrX-129540451-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000276.4(OCRL):c.12G>C(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000955 in 1,151,630 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000083 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )

Consequence

OCRL
NM_000276.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

Variant links:

Genes affected

OCRL (HGNC:8108): (OCRL inositol polyphosphate-5-phosphatase) This gene encodes an inositol polyphosphate 5-phosphatase. This protein is involved in regulating membrane trafficking and is located in numerous subcellular locations including the trans-Golgi network, clathrin-coated vesicles and, endosomes and the plasma membrane. This protein may also play a role in primary cilium formation. Mutations in this gene cause oculocerebrorenal syndrome of Lowe and also Dent disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

OCRL links:

OCRL (HGNC:):

OCRL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant X-129540451-G-C is Benign according to our data. Variant chrX-129540451-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2155424.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.55 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0000831 (9/108300) while in subpopulation AFR AF= 0.000269 (8/29774). AF 95% confidence interval is 0.000133. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OCRL	NM_000276.4 linkuse as main transcript	c.12G>C	p.Pro4Pro	synonymous_variant	1/24	ENST00000371113.9	NP_000267.2	Q01968-1
OCRL	NM_001318784.2 linkuse as main transcript	c.12G>C	p.Pro4Pro	synonymous_variant	1/24		NP_001305713.1	Q504W7
OCRL	NM_001587.4 linkuse as main transcript	c.12G>C	p.Pro4Pro	synonymous_variant	1/23		NP_001578.2	Q01968-2A0A2X0TVZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OCRL	ENST00000371113.9 linkuse as main transcript	c.12G>C	p.Pro4Pro	synonymous_variant	1/24	1	NM_000276.4	ENSP00000360154.4	Q01968-1
OCRL	ENST00000357121.5 linkuse as main transcript	c.12G>C	p.Pro4Pro	synonymous_variant	1/23	1		ENSP00000349635.5	Q01968-2
OCRL	ENST00000691455.1 linkuse as main transcript	n.12G>C		non_coding_transcript_exon_variant	1/18			ENSP00000510265.1	A0A8I5KYX7
OCRL	ENST00000486673.1 linkuse as main transcript	n.91+512G>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000831

AC:

AN:

108265

Hom.:

Cov.:

AF XY:

0.0000652

AC XY:

AN XY:

30685

show subpopulations

Gnomad AFR

AF:

0.000269

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000961

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000104

AC:

AN:

95700

Hom.:

AF XY:

0.00

AC XY:

AN XY:

35102

show subpopulations

Gnomad AFR exome

AF:

0.000207

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000192

AC:

AN:

1043330

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

340808

show subpopulations

Gnomad4 AFR exome

AF:

0.0000808

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000831

AC:

AN:

108300

Hom.:

Cov.:

AF XY:

0.0000651

AC XY:

AN XY:

30730

show subpopulations

Gnomad4 AFR

AF:

0.000269

Gnomad4 AMR

AF:

0.0000960

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lowe syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over